# Novel treatment for respiratory distress due to SARS-CoV2 infection

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $195,625

## Abstract

SUMMARY
Clinical sequelae of COVID-19 patients include not only acute respiratory distress syndrome (ARDS), but also
often acute kidney injury and heart failure. These pathologies share endothelial activation as a common
underlying early response to injury, and endothelial cells express high levels of angiotensin converting enzyme
2 (ACE2), a functional receptor for SARS-CoV-2. Activated endothelium not only attracts and promotes
leukocyte infiltration into tissues and contributes to the cytokine storm resulting in capillary leakage and edema,
but is also prothrombotic. Together, these mechanisms result in tissue inflammation and ischemia, leading to
organ failure. Our laboratory discovered that polymerase delta interacting protein 2 (Poldip2) is a novel and
important regulator of inflammation, endothelial permeability and potentially coagulation in mice. Mice
heterozygous for Poldip2 are largely protected from lipopolysaccharide (LPS)- or P. aeruginosa-induced ARDS.
Here, we hypothesize that Poldip2 may be a novel target for treatment of SARS-CoV-2-infected individuals, as
downregulation of Poldip2 not only reduces ARDS complications such as edema and the cytokine storm, but
also potentially may inhibit thrombosis. To test this hypothesis, we propose to treat SARS-CoV-2-infected mice
with an anti-cancer agent undergoing clinical trials that we have recently shown to reduce Poldip2 levels and
restore endothelial barrier function. In the first Aim, we will use this agent to downregulate Poldip2 and test its
ability to preserve endothelial barrier function and reduce inflammation in response to SARS-CoV-2 infection in
mice. The second aim will focus on determining the effect of the anticancer agent and genetic ablation of Poldip2
on basal coagulation and that induced by SARS-CoV-2 infection. We anticipate that pharmacological
downregulation of Poldip2 will represent a promising new treatment for COVID-19 patients that can be rapidly
translated to the clinic.

## Key facts

- **NIH application ID:** 10426353
- **Project number:** 5R21AI163427-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Cynthia Ann Derdeyn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,625
- **Award type:** 5
- **Project period:** 2021-06-11 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426353

## Citation

> US National Institutes of Health, RePORTER application 10426353, Novel treatment for respiratory distress due to SARS-CoV2 infection (5R21AI163427-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10426353. Licensed CC0.

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